A proposed Shared Instrumentation Grant (SlG) is submitted to acquire a state-of-the-art, user-friendly and fully automated Bioluminescence Imaging System (Xenogen, IVlS). The use of In Vivo Bioluminescence Imaging (IBL) has seen tremendous growth in recent years owing largely to the potential to image light emission (bioluminescence) mediated by luciferase from anywhere within small rodents. This technology may be used in studies of gene expression (using luciferase as reporter gene), infectious diseases (imaging and tracking light emitting bacteria), and transplant studies (imaging and tracking light emitting allografts). This new system is required to replace an existing home-built system based on an intensified CCD camera, which has low sensitivity to the red light used in IBL. The manual controls of all-important imaging parameters make this system difficult to manage in a multi-user environment. In fact, the existing instrument was never intended to be a shared resource, but has become the de facto user system for the University. The proposed IVlS system, which is built around a back-illuminated, back-thinned, cooled, deep depletion CCD camera, will have sensitivity levels for in vivo imaging that are 1-2 orders of magnitude better than the existing system. Further, the proposed system is designed specifically for IBL and is fully computer controlled (using Xenogen's Livinglmage software). This software package controls and logs the working distance, the lens settings (focus and fstop). The system has a heated sample stage inside the imaging chamber, as well as build-in gas anesthesia capabilities. All of these features make the IVlS system ideal for our multi-user needs. The major users of this new instrument include researchers in the fields of cancer (Coffey, Hallahan, Jansen, Lin, Matrisian), diabetes (Piston, Powers, Takahashi), lung diseases (Blackwell), and wound healing (Davidson, Jansen). The major users will account for approximately 70% of the time available on the instrument. As we expect continued growth in IBL, we have also reserved 30% time for minor and new users. The new system will be physically located in the Keck Free Electron Laser Center, which is conveniently located centrally on the Vanderbilt Campus. This multidisciplinary user center houses extensive shared spectroscopy and imaging systems that are routinely used by numerous investigators from the biological sciences, medical sciences, physical sciences, and engineering. Administration and management of the proposed system will be handled under the umbrella of the Cell Imaging Shared Resource (ClSR) which currently manages 10 shared microscopes and imaging systems, including two that are adjacent to the location of this new instrument.